Neoplastic transformation is accompanied by widespread changes in DNA methylation. The most common change involves loss of methylation that leads to transcriptional activation of genes that are unexpressed in normal cells. It has recently been proposed that because of their abundance, high concentration of CpG dinucleotides, and extensive methylation, transposable elements are the site of the majority of 5- methylcytosines in the genome, and that the primary function of cytosine methylation is the suppression of these elements. Such sequences are frequently overexpressed in transformed cells. We have used the IAP proviral family members as reporters for chromosomal regions that undergo changes in methylation in tumors. These proviral elements are 2000-fold reiterated and widely dispersed in the mouse genome, making them ideal for this type of analysis.Increased expression of IAP proviral elements in tumor cells compared with normal cells is accompanied by extensive hypomethylation of IAP sequences. We have used oligonucleotide probes based on sequences in the LTRs of expressed IAP elements to examine the methylation state of subsets of the endogenous IAP proviral sequences, and have found that multiple common IAP loci are hypomelthylated in B-cell tumors. However, not all IAP elements are hypomethylated even when their LTR sequences are very similar, suggesting that the methylation state of the proviral DNA is determined by their position in the genome. We have now mapped a number of the commonly hypomethylated loci in B-cell tumors. These include regions on chromosome 2, 4, 5, 7, 13, 16, 17, and 18. Previously, attempts to isolate DNA regions flanking these loci had been unsuccessful. However, BAC libraries carrying large inserts of mouse DNA have recently become available, making it possible to more easily isolate genomic regions of interest. A number of BAC clones carrying IAP elements that undergo changes in methylation in tumors are currently being analyzed to characterize the flanking sequences, which may play a role in the malignant phenotype. - genetic linkage analysis, Intracisternal A-particles, lymphocytes, Transformation, - Neither Human Subjects nor Human Tissues